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Sichuan University

Verified scientific contributions, CAS laboratory outputs, clinical trial papers, and engineering breakthroughs produced by researchers and faculty affiliated with Sichuan University.

Stem Cell Research & Therapy•2026

Stem cell-driven biomedical technologies for tooth regeneration: engineering scaffolds, organoid models, and molecular targeted strategies

Authors: Zhaorui Jin, Bo Yang, Siyuan Zhang, Zhi Liu, Yuhao Wang, An Lin, Kexin Yang, Mei Yu, Weidong Tian, Fangjun Huo

Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.

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Chinese Journal of Tissue Engineering Research•2026

Cobalt chloride-induced hypoxic environment accelerates knee cartilage degeneration in New Zealand rabbits

Authors: XU Peng, JIANG Wei, YU You, LEI Zhengliang, TIAN Yang, ZHANG Jie, LIU Luchang

BACKGROUND: Cobalt chloride solution is commonly used to induce osteoarthritis cell models in vitro. However, its ability to construct animal models of osteoarthritis by intra-articular injection remains unknown. OBJECTIVE: To investigate the effect of intra-articular injection of different concentrations of cobalt chloride solution on cartilage degeneration in the knee joint. METHODS: Thirty-six healthy adult male New Zealand rabbits were randomly divided into four groups: low, medium and high dose cobalt chloride groups and control group. The right hind knee was intra-articularly injected with 100, 200, and 300 μmol/(L·kg) of cobalt chloride, while the left hind knee served as the control knee and was injected with an equal amount of normal saline. At 4, 8 and 12 weeks after operation, four rabbits were killed respectively. The cartilage on the surface of the femur was exposed for gross morphological observation, and then the cartilage tissues were taken for hematoxylin-eosin staining, safranine O-fast green staining, the Osteoarthritis Research Society International scoring, and immunohistochemical staining of interleukin 1 and tumor necrosis factor α, to determine cartilage degeneration in various aspects. RESULTS AND CONCLUSION: (1) Gross observation: At the same postoperative time point, with the increase of cobalt chloride concentration, cartilage degeneration showed a progressive aggravation trend, and the high-dose cobalt chloride group even involved the deep layer of cartilage and subchondral bone; under the same concentration of cobalt chloride, with the prolongation of modeling time, cartilage degeneration progressed progressively. (2) Hematoxylin-eosin staining, safranine O-fast green staining, and Osteoarthritis Research Society International scoring showed that at the same postoperative time point, with the increase of cobalt chloride concentration, the cartilage surface gradually became rough, the superficial layer became thinner, and the destruction aggravated, and the Osteoarthritis Research Society International score gradually increased (P < 0.05); under the same concentration of cobalt chloride, with the prolongation of modeling time, the arrangement of chondrocytes tended to be disordered, polarity was lost, and the destruction of superficial cartilage and subchondral bone progressively aggravated, and the Osteoarthritis Research Society International score gradually increased (P < 0.05). (3) Immunohistochemistry showed that at the same postoperative time point, with the increase of cobalt chloride concentration, cartilage degeneration aggravated, intracellular brown particles increased, and the positive expression of interleukin 1 and tumor necrosis factor α increased (P < 0.01); under the same concentration of cobalt chloride, with the prolongation of modeling time, cartilage destruction and fissures aggravated, and the positive expression of interleukin 1 and tumor necrosis factor α increased (P < 0.01). This experiment successfully established an osteoarthritis model of New Zealand rabbits induced by intra-articular injection of cobalt chloride solution, preliminarily verified the stability and reliability of the animal model, and also proved that with the increase of modeling concentration and the prolongation of modeling time, cartilage degeneration progressed progressively.

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Chinese Journal of Tissue Engineering Research•2026

Methylation alterations of Fbln1 gene in the hippocampus of PSEN1/PSEN2 double knockout and APP/PS1 transgenic mice

Authors: Ruan Sibei, Li Li, Jian Yue, Ling Feng, Tang Mingxi

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by abnormal deposition of β-amyloid (Aβ) and neurofibrillary tangles of tau protein. Current medications only alleviate some symptoms, and despite extensive efforts to develop new therapies, such as anti-Aβ immunotherapy and β-secretase inhibitors, clinical trials have not been successful. OBJECTIVE: To investigate the methylation changes of the Fbln1 gene in the hippocampus of PSEN1/PSEN2 double knockout (dKO) mice, which lack Aβ deposition, and APP/PS1 double transgenic (DTG) mice, which exhibit Aβ deposition, to explore non-Aβ-related mechanisms and potential targets in AD. METHODS: Hippocampal tissues were collected from female dKO mice at 7 months (early AD) and 12 months (mid-stage AD) of age, with age-matched wild-type (WT) mice as controls. Epigenetic reduced representation bisulfite sequencing (RRBS) was used to screen for aberrantly methylated genes, identifying Fbln1. Bisulfite sequencing PCR (BSP) was performed to validate the methylation status of Fbln1 in mid-stage dKO mice. RT-PCR and western blot were used to measure Fbln1 mRNA and protein expression in early and mid-stage dKO mice, as well as in 12-month-old DTG mice. Finally, the expression levels of Fbln1 and Aβ were compared between dKO and DTG mice, with age-matched WT mice as controls. RESULTS AND CONCLUSION: RRBS showed that Fbln1 was hypomethylated in the hippocampus of mid-stage dKO mice (P < 0.05), while early-stage dKO mice showed a trend of hypomethylation but without statistical significance (P > 0.05). BSP confirmed the abnormal hypomethylation of Fbln1 in mid-stage dKO mice. In early-stage dKO mice, Fbln1 mRNA and protein levels were not significantly different from WT (P > 0.05). In mid-stage dKO mice, Fbln1 mRNA and protein levels were significantly higher than in WT (t=5.336, P < 0.01; t=8.985, P < 0.01). Similarly, mid-stage DTG mice showed significantly higher Fbln1 mRNA and protein levels than WT (t=4.151, P < 0.01; t=8.392, P < 0.01), but there was no significant difference between the two AD models (P > 0.05). In mid-stage dKO mice, there was no significant difference between Fbln1 and Aβ protein levels (P > 0.05), whereas in DTG mice, the difference was significant (t=6.348, P < 0.01), indicating that Fbln1 plays a role in both Aβ-dependent and Aβ-independent mechanisms. These findings suggest that Fbln1 methylation changes may contribute to age-dependent neurodegeneration in dKO mice and may be involved in both Aβ and non-Aβ pathways in AD, providing new insights and potential targets for non-Aβ-related mechanisms. Fbln1, as an aging-related factor, holds promise as a novel target.

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Chinese Journal of Tissue Engineering Research•2026

Impact of disease duration on lumbar curvature correction in patients with rigid post-traumatic thoracolumbar kyphosis

Authors: Yang Junjie, Zhang Hao, Chen Zhike, Chen Yao, Jia Bingxu, Wang Qing, Li Guangzhou, Wang Gaoju

BACKGROUND: Currently, most studies on rigid post-traumatic thoracolumbar kyphosis focus on overall sagittal balance and surgical intervention, while the effect of the disease duration on the change of lumbar compensatory curvature and degeneration is still unclear. OBJECTIVE: To explore the effect of the disease duration on lumbar degeneration and the potential mechanism of rigid post-traumatic thoracolumbar kyphosis in patients with rigid post-traumatic thoracolumbar kyphosis, and provide a basis for optimizing treatment strategies. METHODS: Clinical and imaging data from 79 rigid post-traumatic thoracolumbar kyphosis patients were retrospectively analyzed. The patients were divided into two groups according to the disease duration: Patients with a disease duration of ≤ 5 years were categorized as group A (n=40), and those with > 5 years as group B (n=39). X-ray images were used to measure the local kyphosis angle of the injured vertebra, the height of the posterior walls of the injured vertebra and adjacent vertebrae, lumbar lordosis, the intervertebral space angle for each lumbar segment, and sacral slope. The Weishaupt-CT classification system was employed to assess lumbar facet joint degeneration. Pfirrmann-MRI grading was used to evaluate intervertebral disc degeneration. Clinical outcomes including visual analog scale for back pain, Oswestry Disability Index, SRS-22 score, and American Spinal Injury Association impairment scale were compared between groups. The influence of disease duration on clinical symptoms and imaging features was analyzed. RESULTS AND CONCLUSION: (1) There were no significant differences in age, sex, visual analog scale score, fracture site, fracture morphology, or American Spinal Injury Association grade between the two groups (P > 0.05). The SRS-22 subscore was significantly higher in group A than in group B (P < 0.05), while the Oswestry Disability Index was significantly higher in group B than in group A (P < 0.05). (2) The local kyphosis angle, lumbar lordosis, and L4/5 intervertebral space angle were significantly greater in group B than in group A (P < 0.05). (3) There were no significant differences in L1/2, L2/3, L3/4, L5/S1 intervertebral space angles and sacral slope between groups (P > 0.05). (4) The degree of facet joint degeneration at L3/4, L4/5, and L5/S1 was significantly more severe in group B than in group A (P < 0.05). The degree of intervertebral disc degeneration at L2/3, L3/4, L4/5, and L5/S1 was significantly more severe in group B than in group A (P < 0.05). (5) Pearson correlation analysis showed that within group B, disease duration was positively correlated with local kyphosis angle and lumbar lordosis (r=0.335, 0.418, P < 0.05). (6) In patients with rigid post-traumatic thoracolumbar kyphosis, long-term compensation leads to increased lumbar lordosis and accelerated lumbar degeneration. The L4/5 segment is the main compensatory segment in lumbar curvature compensation, and special attention should be paid to the correction of lower lumbar curvature during surgical correction.

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Chinese Journal of Tissue Engineering Research•2026

Bibliometric analysis of application of artificial intelligence in orthopedic imaging diagnosis

Authors: Yue Yuhang, Xie Liangyu, Shi Liupeng, Yin Zuozhen, Cao Shengnan, Shi Bin, Sun Guodong

BACKGROUND: In the process of applying artificial intelligence to orthopedic imaging, the technical system exhibits a clear hierarchical structure: machine learning is the primary pathway to achieving artificial intelligence, while convolutional neural networks, a branch of deep learning, have become the core model for image analysis. Clarifying this technical lineage helps to systematically review the research evolution and trends in this field through bibliometric methods. OBJECTIVE: To comprehensively analyze the research status and development trends of artificial intelligence in the field of orthopedic imaging based on bibliometric methods, providing ideas and methods for future research. METHODS: By searching the Web of Science Core Collection database, with keywords including artificial intelligence, deep learning, convolutional neural network, and orthopedic imaging, a total of 460 relevant English articles published between 2015 and 2025 were included. CiteSpace 6.4.R1, VOSviewer 1.6.20, and Bibliometrix software were used to conduct visual analysis from dimensions such as annual publication volume, country and institution distribution, author collaboration network, keyword co-occurrence, clustering, and burst word evolution. RESULTS AND CONCLUSION: (1) The number of publications in this field has steadily increased over the past 10 years. (2) China and the United States are the main publishing countries, with the United States showing outstanding performance in citation frequency and international collaboration influence; Sichuan University, the University of California, and Harvard University constitute a core collaborative institutional network. (3) Research hotspots mainly focus on bone age assessment, automated image segmentation, and the application of deep learning in fracture detection and osteoarthritis diagnosis. Related keywords such as bone age assessment, automated segmentation, and deep learning have continued to burst, indicating the evolutionary trajectory of research focus. (4) The research enthusiasm for artificial intelligence in orthopedic imaging continues to rise, with intelligent segmentation, disease grading, and multimodal data fusion being important future research directions. (5) This paper systematically reviews the field from a macro perspective, providing a reference for promoting the deep integration of artificial intelligence technology in orthopedic clinical practice; through bibliometric analysis, it constructs a knowledge map of the application of artificial intelligence in orthopedic imaging, systematically summarizes the research status and hotspots in this field, and aims to provide reference and guidance for future related research.

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Chinese Journal of Tissue Engineering Research•2026

Shaoyang Shenggu Fang inhibits oxidative stress and delays cartilage aging in rats with knee osteoarthritis

Authors: Yong Qiao, Xin Sun, Guoyou Wang, Lei Zhang, Huarui Shen, Huan Liu, Taiyuan Guan

BACKGROUND: Preliminary studies have demonstrated that Shaoyang Shenggu Fang can alleviate joint cartilage degeneration and promote cartilage repair, but its specific mechanism for alleviating knee osteoarthritis symptoms remains unclear. The Wnt/β-catenin pathway and oxidative stress play crucial roles in maintaining articular cartilage homeostasis. OBJECTIVE: To investigate the molecular mechanisms by which Shaoyang Shenggu Fang regulates the Wnt/β-catenin pathway to inhibit oxidative stress in cartilage and thereby delay cartilage aging in a rat model of knee osteoarthritis. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups: a blank control group, a model group, a Western medicine group, and a Chinese medicine group. Animal models of knee osteoarthritis were established in all groups except for the blank control group by transecting the anterior cruciate ligament and resecting the anterior horn of the medial meniscus. After 28 days of modeling, the Chinese medicine group was administered concentrated Shaoyang Shenggu Fang at a dose of 16 g/(kg·d) by gavage, the Western medicine group received glucosamine hydrochloride solution at 4 mL/d, and the blank and model groups received the same volume of normal saline. After 4 weeks, hematoxylin-eosin staining and Safranin O-fast green staining were used to observe the degree of cartilage damage and degeneration. ELISA was used to detect serum levels of inflammatory factors and oxidative stress indicators. Western blot was used to detect the expression of p21Cip1, p16INK4a, and Wnt signaling pathway-related proteins in knee cartilage. RESULTS AND CONCLUSION: Compared with the model group, the Western medicine and Chinese medicine groups showed significant improvement in cartilage defects, thinning of the cartilage layer, and decreased density, with significantly lower Mankin scores (P < 0.05). Compared with the model group, serum levels of interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased in the Western medicine and Chinese medicine groups (P < 0.05), while superoxide dismutase and glutathione peroxidase levels were increased and malondialdehyde concentration was decreased (all P < 0.05). In the Chinese medicine group, the expression levels of p21Cip1, p16INK4a, and Wnt5a proteins were significantly decreased (P < 0.05 and P < 0.01), β-catenin and C-Myc protein expression levels were decreased (P < 0.05), and glycogen synthase kinase-3β protein expression was significantly increased (P < 0.05). These results suggest that Shaoyang Shenggu Fang can significantly reduce inflammation and alleviate cartilage aging in rats with knee osteoarthritis, and the potential mechanism may be through regulation of the Wnt/β-catenin pathway to inhibit cartilage oxidative stress.

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Chinese Journal of Tissue Engineering Research•2026

Culture and identification of adipose-derived stem cells from periprostatic adipose tissue

Authors: Zhou Shukui, Liu Jinpeng, Gao Wenlong, Yang Shengke, Liao Hong, Wu Yi, Li Zeng

BACKGROUND: Periprostatic adipose tissue is the white visceral adipose tissue that is closest to the prostate, which is part of the prostate cancer tumor microenvironment and plays a key role in the occurrence and progression of prostate cancer. OBJECTIVE: To investigate the ability of adipose-derived stem cells derived from periprostatic adipose tissue to form three-dimensional cell sheets. METHODS: Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy. Adipose-derived stem cell suspensions were prepared using a combination of enzymatic digestion and mechanical dissection. Adipose-derived stem cell proliferation was assessed using a CCK-8 assay. Expression of stem cell-associated antigens CD34/CD44/CD45/CD90/CD105 was determined by flow cytometry. Multidirectional differentiation potential of the stem cells was assessed using osteogenic/adipogenic/chondrogenic differentiation assays. Adipose-derived stem cells were cultured for three weeks in low-glucose DMEM containing 100 ÎĽg/mL vitamin C and 10% fetal bovine serum to construct cell sheets, followed by histological analysis and scanning electron microscopy. RESULTS AND CONCLUSION: Adipose-derived stem cells from periprostatic adipose tissue exhibited a long spindle or fusiform shape, aligned growth, and consistent morphology. Primary culture reached 95% confluence at 9-10 days with good cell viability, and no obvious senescence was observed up to passage 15. Flow cytometry showed expression rates of CD44, CD90, and CD105 at 98.24%, 84.99%, and 89.14%, respectively, while CD34 and CD45 were expressed at 0.64% and 1.02%. After 3 weeks of osteogenic, adipogenic, and chondrogenic induction, the cells could differentiate into osteoblasts, adipocytes, and chondrocytes. After continuous culture for 3 weeks, the cells formed a three-dimensional cell sheet with a smooth surface and uniform texture, rich in extracellular matrix components such as fibronectin and type I collagen. Scanning electron microscopy revealed a flat surface with aligned long spindle-shaped cells and abundant extracellular matrix deposition between cells. This study successfully isolated adipose-derived stem cells from periprostatic adipose tissue of prostate cancer patients and constructed a three-dimensional cell sheet by stimulating extracellular matrix secretion with vitamin C over 3 weeks of continuous culture.

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Chinese Journal of Tissue Engineering Research•2026

Research status and trends of nanotechnology in improving photodynamic therapy for hypoxic tumors

Authors: Dilida·Bahetikelede, Zhou Xin, Wang Xinyi, Zeng Zhihan, Wang Liqiong, Hu Danrong

BACKGROUND: Photodynamic therapy, a novel tumor treatment, is limited by the hypoxic tumor microenvironment. Nanotechnology-based oxygen regulation strategies offer a novel approach to overcoming this bottleneck. OBJECTIVE: To systematically analyze the research status of nanotechnology in improving photodynamic therapy for hypoxic solid tumors using bibliometric methods, identify hotspots, and predict future directions. METHODS: Publications and reviews from 2016 to 2025 on nanotechnology for regulating tumor hypoxia and enhancing photodynamic therapy were retrieved from the Web of Science Core Collection. Excel, CiteSpace, VOSviewer, and Bibliometrix were used for visual analysis of categories, publication trends, countries, institutions, authors, co-cited references, and keywords. RESULTS AND CONCLUSION: A total of 1,879 articles were included, with 'nanoscience & nanotechnology' as the core category. From 2016 to 2022, publications increased steadily, with a slight decline in 2023 and a subsequent rise. China was the leading country, with the Chinese Academy of Sciences having the highest output, and Liu Zhuang from Soochow University being the most prolific author. The most cited paper was by Zhou ZJ et al. (2016) in Chemical Society Reviews. The field focuses on cancer treatment, particularly microenvironment-responsive optical therapeutic strategies using nanomaterials. Keywords 'Photodynamic therapy' and 'Nanoparticles' appeared most frequently. Bibliometric analysis indicates that nanotechnology offers advantages in enhancing photodynamic therapy for hypoxic tumors, with promising efficacy and safety. Future hotspots may focus on combination with immunotherapy.

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Chinese Journal of Tissue Engineering Research•2026

Lentivirus-mediated gene therapy in a beta-thalassemia mouse model

Authors: Liu Hongwei, Chang Lungji

BACKGROUND: Lentiviral vector (LV)-mediated autologous hematopoietic stem cell gene therapy is expected to be a novel curative treatment for β-thalassemia. The LV serves as a core agent of gene therapy, directly influencing future clinical efficacy and treatment costs. Therefore, the primary task is to develop high-performance lentiviral vectors. OBJECTIVE: To explore the feasibility of an ex vivo gene therapy and assess the activity and functionality of the β-globin-LV in thalassemic mice. METHODS: A novel lentiviral vector, HS40-LV, carrying the human β-globin gene cassette, was constructed. 7.5 Gy-conditioned Hbbth3/+ mice were subjected to HS40-LV-modified hematopoietic stem cell transplantation. Normal mice and untreated thalassemic mice served as controls. Peripheral blood samples were collected from mice at 2, 4, 6, 8, and 10 months post-treatment. The integrated proviral DNA in the individual sample was detected by using qPCR. The proportion of red blood cells expressing human β-globin was detected by fluorescence-activated cell sorting. Fresh whole blood was collected for blood smears, which were used for Giemsa staining, reticulocyte staining, and fully automated blood cell analysis. At 10 months post-treatment, the liver, spleen, and bone marrow tissues were sampled from all three groups to prepare single-cell suspensions and extract genomic DNA for qPCR detection of vector marking; flow cytometry was used to detect cells expressing transgenic β-globin; portions of spleen and liver were subjected to hematoxylin-eosin staining and Prussian blue staining. RESULTS AND CONCLUSION: (1) The HS40-LV vector achieved a transduction efficiency of 50% in hematopoietic stem cells. (2) During the 10-month follow-up, the proportion of vector-marked cells and β-globin-positive red blood cells in peripheral blood of treated mice steadily increased, reaching an average of 50% vector marking and 70% β-globin-positive red blood cells at 10 months post-transplantation. (3) Biological distribution of the lentiviral vector and expression of transgenic β-globin were also detected in liver, spleen, and bone marrow hematopoietic tissues. (4) Gene therapy corrected hematological parameters in thalassemic mice, such as significant reductions in poikilocytes, reticulocytes, and cell fragments, and a significant increase in overall hemoglobin levels. (5) Histopathological improvements were also observed, with significant reductions in iron deposition in spleen and liver, and improved extramedullary hematopoiesis. These results indicate that the novel HS40-LV vector achieved stable expression in vivo, and modified cells corrected some symptoms in thalassemic mice.

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Chinese Journal of Tissue Engineering Research•2026

Application of novel materials in tissue repair of diabetic foot wounds

Authors: Xia Jinyan, Su Meifang, Yang Wenyu, Hu Qilan, Gong Li

BACKGROUND: In recent years, the convergence of materials science and biomedical engineering has opened new avenues for diabetic foot wound treatment. Novel biomaterials such as multifunctional hydrogels, tissue engineering scaffolds, and nanoparticle systems have become a research hotspot. OBJECTIVE: To analyze, through bibliometric analysis, the design principles and biological functions of novel materials used in diabetic foot wound treatment, their potential in addressing the complex pathological challenges of diabetic foot, and to forecast future directions and challenges in this field. METHODS: We searched the Web of Science database for literature on novel materials for diabetic foot wounds from database inception to June 2025, and used CiteSpace software for bibliometric visualization analysis. RESULTS AND CONCLUSION: From 1979 to 2025, the number of publications in the field of novel materials for diabetic foot wound treatment showed an overall fluctuating upward trend, with explosive growth from 2022 to 2025. The United States ranked first with 602 publications, followed by China (284 publications) and India (166 publications). By publication count, Sichuan University had the most publications, followed by Tehran University of Medical Sciences; by citation impact, Sichuan University had the highest total citation impact, followed by Nankai University. West China Hospital ranked first in publication count, followed by Beth Israel Deaconess Medical Center and Thomas Jefferson University Hospital; by citation impact, West China Hospital had the highest impact, followed by Shanghai Ninth People's Hospital and Thomas Jefferson University Hospital. Among companies, Success Bio-Tech Co. Ltd, Engineering Software Research and Development Inc, and Foot and Ankle Associates of Central Illinois LLC each had 2 publications, ranking first; by citation impact, Organogenesis Inc had the highest impact, followed by Food Industry Research Co. The journal Wounds had the most publications (96), followed by Foot Ankle Int (40) and Cureus (38). Among authors, Bus, Sicco A had the most publications (12), followed by Lázaro-Martínez, José Luis (8); by citation impact, GBD 2021 US Burden of Disease and Forecasting Collaborators, GBD 2021 Diabetes Collaborators, GBD 2021 US Obesity Forecasting Collaborators, GBD 2021 US Burden of Disease Collaborators, GBD 2021 Adult BMI Collaborators, GBD 2021 Adolescent BMI Collaborators, and GBD 2021 Causes of Death Collaborators had the highest impact. Keywords: diabetic foot; diabetic foot wound; diabetic foot ulcer; biomaterials; dressing; visualization analysis.

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Chinese Journal of Tissue Engineering Research•2026

Performance of calcium sulfate-magnesium oxide composites as anti-infective bone graft materials

Authors: HU Liqun, XIAO Dongqin, MA Chenxi, LI Zhuohan, YAN Jiyuan, LI Zhong, HE Kui, DUAN Ke

BACKGROUND: Calcium sulfate bone graft materials have good biocompatibility but lack antibacterial properties, potentially leading to infections. Magnesium oxide has antibacterial effects and can promote bone regeneration and angiogenesis. OBJECTIVE: To develop novel calcium sulfate-magnesium oxide bone graft materials with antibacterial properties and the ability to promote bone regeneration, and to systematically evaluate its antibacterial capabilities, cytocompatibility, and osteogenic and angiogenic potential. METHODS: (1) α-Calcium sulfate hemihydrate was synthesized by a hydrothermal method. α-Calcium sulfate hemihydrate was mixed with magnesium oxide at mass ratios of 2.5%, 7.5%, 15%, and 25%, and distilled water was added to form calcium sulfate-magnesium oxide composites, denoted as CS-2.5MgO, CS-7.5MgO, CS-15MgO, and CS-25MgO. The surface morphology, compressive strength, in vitro degradation, and H2O2 production in PBS were characterized. (2) Escherichia coli (or Staphylococcus aureus) suspensions were co-cultured with the five groups of materials, and antibacterial properties were evaluated by agar plate coating and inhibition zone tests. (3) MC3T3 cells were co-cultured with material extracts, and cytocompatibility was assessed by CCK-8 and live/dead staining. After osteogenic induction, alkaline phosphatase staining and alizarin red staining were used to evaluate osteogenic mineralization, and Western blot detected RUNX2 and WNT3a protein expression. (4) Human umbilical vein endothelial cells were co-cultured with material extracts, and angiogenic potential was evaluated by Matrigel tube formation assay, and Western blot detected endothelial nitric oxide synthase protein expression. (5) α-Calcium sulfate hemihydrate, CS-2.5MgO, CS-7.5MgO, CS-15MgO, and CS-25MgO loaded with Staphylococcus aureus were implanted into muscle incisions of SD rats. At 1, 3, and 7 days postoperatively, materials and adjacent muscle tissues were rinsed, and the rinse fluid was collected for colony counting by agar plate coating. Hematoxylin-eosin staining was used to observe inflammatory cell infiltration in surrounding muscle tissues. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that α-calcium sulfate hemihydrate mostly exhibited short rod-like crystals with a few long strip crystals and smooth surfaces; in the composites, magnesium oxide particle aggregates were distributed on crystal surfaces and between crystals, with density increasing with magnesium oxide ratio. Compared with α-calcium sulfate hemihydrate, the compressive strength and degradation rate of the composites decreased, while H2O2 production in PBS increased. Agar plate coating and inhibition zone tests showed that the composites had excellent antibacterial properties, which increased with magnesium oxide ratio. CCK-8 and live/dead staining showed that α-calcium sulfate hemihydrate, CS-2.5MgO, and CS-7.5MgO had good cytocompatibility. Alkaline phosphatase staining, alizarin red staining, and Western blot showed that CS-2.5MgO enhanced osteogenic mineralization. Matrigel tube formation and Western blot showed that CS-7.5MgO had the strongest angiogenic ability. (2) Rinse fluid agar plate coating showed that the composites had good in vivo antibacterial properties compared with α-calcium sulfate hemihydrate, increasing with magnesium oxide ratio. Hematoxylin-eosin staining showed that inflammatory cell infiltration and exudation in muscle tissues were significantly reduced in all composite groups compared with α-calcium sulfate hemihydrate group. (3) These results indicate that calcium sulfate-magnesium oxide composites have good cytocompatibility and antibacterial properties, and can effectively promote osteogenesis and angiogenesis.

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Stem Cell Research & Therapy•2026

Stem cell-driven biomedical technologies for tooth regeneration: engineering scaffolds, organoid models, and molecular targeted strategies

Authors: Zhaorui Jin, Bo Yang, Siyuan Zhang, Zhi Liu, Yuhao Wang, An Lin, Kexin Yang, Mei Yu, Weidong Tian, Fangjun Huo

Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.

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Acta Biochimica et Biophysica Sinica•2026

How Distinct Hormones Sculpt a Common Receptor: Ligand-Specific Conformational Pathways of the Insulin Receptor

Authors: JIANG Di, TANG Dan, QI Shiqian

The insulin receptor (IR) is a central regulator of metabolism, integrating hormonal cues to coordinate glucose uptake, lipid metabolism, growth, and survival. While insulin is its canonical ligand, IR also responds to insulin-like growth factors (IGF-I and IGF-II) with lower affinity, a cross-reactivity that is physiologically relevant during development and pathologically important in cancer. Despite extensive research, the molecular basis for how distinct hormones engage the same receptor yet elicit different activation modes remained unresolved. In this study, Yan and colleagues determined the first cryo-electron microscopy (cryo-EM) structures of full-length human IR-A bound to IGF-I, alongside those with insulin and IGF-II, under matched experimental conditions. By capturing multiple ligand-occupancy and conformational states, they revealed that insulin and IGFs drive distinct conformational trajectories through a shared architectural framework, reframing IR activation as a ligand-dependent conformational selection process. Insulin rapidly stabilizes the receptor head region, minimizing conformational heterogeneity and promoting synchronized activation, consistent with its fast, concentration-dependent physiological actions. In contrast, IGF-I and IGF-II induce greater conformational plasticity and a pronounced preference for asymmetric intermediate states, favoring sustained and adaptable engagement suited to long-term growth and differentiation. Site-specific analysis showed that while core residues are shared, insulin forms a denser hydrogen-bond network at site 1, whereas IGFs rely more on secondary sites. These findings provide a structural basis for ligand-specific cooperativity and signaling bias, with implications for understanding metabolic diseases and cancer, and for designing selective IR modulators.

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Acta Biochimica et Biophysica Sinica•2026

METTL3-mediated m6A modification facilitates Nectin-4-induced VNN1 upregulation and promotion of ESCC progression

Authors: Yuanfeng Long, Hang Yang, Ruolan Zhang, Quanneng Zhao, Mi Yang, Guiqin Song, Kang Liu

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. N6-methyladenosine (m6A) RNA modification plays a role in tumorigenesis, but its contributions to ESCC and the regulation of cell adhesion molecules such as Nectin-4 are not fully elucidated. In this study, we investigate the role and the regulatory mechanisms of Nectin-4 in ESCC, particularly regarding the influence of m6A modification and its downstream metabolic effects. Our study demonstrates that methyltransferase-like protein 3 (METTL3) enhances Nectin-4 mRNA stability and expression through m6A methylation in ESCC, as validated by actinomycin D assay, MeRIP-qPCR, and dual-luciferase reporter assay. Both METTL3 and Nectin-4 are highly expressed in ESCC tissues and promote malignant phenotypes such as proliferation, migration, and invasion. Further analysis identifies pantothenate esterase 1 (VNN1) as a downstream target of Nectin-4, mediating the oncogenic effects of the METTL3/Nectin-4 axis and promoting the biosynthesis of pantothenic acid and coenzyme A, thus driving ESCC progression. By integrating transcriptomic data, this study elucidates a key pathogenic mechanism in which the METTL3/Nectin-4/VNN1 axis regulates metabolic reprogramming to promote ESCC development. These findings provide new insights into the molecular pathology of ESCC and offer potential biomarkers and therapeutic targets for early screening, prognosis, and precision treatment for ESSC.

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Acta Biochimica et Biophysica Sinica•2026

FGF8 promotes lipid droplet accumulation via the FGFR1/p-p38 axis in chondrocytes

Authors: Minglei Huang, Haoran Chen, Jieya Wei, Caixia Pi, Mengmeng Duan, Xiaohua Pu, Zhixing Niu, Siqun Xu, Shasha Tu, Sijun Liu, Jiazhou Li, Li Zhang, Yang Liu, Hao Chen, Chunming Xu, Jing Xie

Chondrocytes store lipids in the form of lipid droplets (LDs) and maintain cartilage lipid metabolic homeostasis by consuming or regenerating LDs. This modulation is largely mediated by a series of biochemical factors. Fibroblast growth factor 8 (FGF8) is one of the most important factors involved in the proliferation, differentiation, and migration of chondrocytes and has attracted increasing attention in the physiology and pathology of cartilage. However, the effect of FGF8 on LD accumulation in chondrocytes remains unclear. This study aims to elucidate the role of FGF8 in LDs and explore the underlying biomechanism involved. The results reveal that FGF8 promotes LD accumulation in chondrocytes by upregulating perilipin1 (Plin1) expression. FGF8 activates the cytoplasmic p-p38 signaling pathway via fibroblast growth factor receptor 1 (FGFR1) to increase LD accumulation in chondrocytes. Subsequent experiments with siRNAs and specific inhibitors further confirm the importance of the FGFR1/p38 axis for LD accumulation in chondrocytes exposed to FGF8. The results increase our understanding of the role of FGF8 in the lipid metabolic homeostasis of chondrocytes and provide insights into the physiology and pathology of cartilage.

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Acta Biochimica et Biophysica Sinica•2026

Energy stress and adaptation strategy of tumor cells in different microenvironments: from primary tumors to distant metastases

Authors: Mingzhe Xu, Junjie Fei, Zhi-Xiong Xiao, Yong Yi

Since the Warburg effect was first described in the 1920s, tumor energy metabolism has been a central focus of cancer research, emerging as a potential therapeutic target. The tumor microenvironment—including blood vessels, immune cells, stromal components, and other cell types—profoundly influences tumor cell metabolism. Variations in energy supply, oxygen availability, nutrient composition, and the accumulation of metabolic waste across different microenvironments challenge tumor cell survival and progression. In response, tumor cells adapt through flexible regulation and reprogramming of metabolic pathways. Although recent studies have explored metabolic adaptation mechanisms in various tumor microenvironments, the full spectrum from primary tumors to distant metastases remains unexplored. This review summarizes energy stress and adaptation maneuvers in tumor cells across different stages of tumor progression and offers a new perspective for comprehensive research to explore therapeutic strategies targeting tumor metabolism.

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Acta Biochimica et Biophysica Sinica•2026

Crosstalk between YAP/TAZ and ERα in mechanical and hormonal signaling in the skeletal system

Authors: Ruiying Han, Tianyi Wang, Yikai He, Ding Bai, Jing Xie, Yongwen Guo

Bone remodeling represents a dynamic equilibrium orchestrated by mechanobiological and endocrine signals, with YAP/TAZ and ERα emerging as pivotal regulators of skeletal adaptation. YAP/TAZ functions as the central mechanotransduction hub of the Hippo pathway, converting biomechanical cues, including microenvironment matrix stiffness and shear stress, into osteogenic transcriptional programs. Concurrently, ERα integrates both mechanical stimuli and estradiol (E2) signaling to coordinate osteoblast-osteoclast coupling through the transcriptional regulation of RUNX2 activity and RANKL suppression. Although increasing evidence suggests that these two systems might engage in functional crosstalk, there is still no consensus on this issue. This review synthesizes the current understanding of YAP/TAZ-ERα interactions across three dimensions: (1) mechanohormonal integration in skeletal remodeling, (2) context-dependent reciprocity in breast carcinogenesis, and (3) tissue-specific regulatory paradigms in extra-skeletal systems. Key findings reveal that YAP/TAZ and ERα exhibit both synergistic cooperation (enhanced osteogenic differentiation via promoter co-occupancy) and pathway antagonism (competitive TEAD binding), with their interaction dynamics being critically shaped by the cellular microenvironmental context. Notably, mechanical potentiation of ERα transcriptional activity requires YAP/TAZ co-activation in bone mesenchymal stem cells, whereas estrogen signaling modulates YAP mechanosensitivity through cytoskeletal remodeling. These mechanistic insights indicate that the YAP/TAZ-ERα axis is a promising therapeutic target for osteoporotic bone loss, particularly in alveolar bone preservation. By bridging endocrine and mechanobiological perspectives, this work provides a conceptual framework for developing combinatorial therapies that simultaneously address hormonal imbalance and mechanical insufficiency in skeletal pathologies.

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Acta Biochimica et Biophysica Sinica•2025

D-CAPS: an efficient CRISPR-Cas9-based phage defense system for E. coli

Authors: Mingjun Sun, Jie Gao, Hongjie Tang, Hengyi Wang, Liyan Zhou, Chuan Song, Yongqiang Tian, Qi Li

Escherichia coli is widely used in industrial chemical synthesis but faces significant challenges due to bacteriophage contamination, which reduces product quality and yield. Therefore, developing an efficient antiphage system is essential. In this study, we develop a CRISPR-Cas9-based antiphage system (CAPS) targeting essential genes of the T7 phage (gene 5 and gene 19) with single gRNAs transformed into MG1655 strains expressing Cas9. While CAPS provides limited resistance, with plating efficiencies ranging from 10–5 to 10–1, further optimization is needed. To enhance efficacy, we design a double-site-targeting CRISPR-Cas9-based antiphage system (D-CAPS). D-CAPS demonstrates complete resistance, with no plaques observed even at a high multiplicity of infection (MOI of 2), and growth curve analysis reveals that antiphage E. coli strains grow normally, similar to the wild-type strain, even at a high multiplicity of infection. Furthermore, D-CAPS is effective against BL21(DE3) strains, showing strong resistance and demonstrating its versatility across different E. coli strains. Protein expression analysis via green fluorescent protein confirms that E. coli carrying D-CAPS could maintain normal protein expression levels even in the presence of phages, comparable to wild-type strains. Overall, D-CAPS offers a robust and versatile approach to enhancing E. coli resistance to phages, providing a practical solution for protecting industrial E. coli strains and improving fermentation processes.

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Acta Biochimica et Biophysica Sinica•2025

Epigallocatechin-3-gallate inhibits osteogenic differentiation of vascular smooth muscle cells through the transcription factor JunB

Authors: Tiantian Li, Fei Fang, Hongmei Yin, Zhen Zhang, Xiangxiu Wang, Erxiang Wang, Hongchi Yu, Yang Shen, Guixue Wang, Weihong He, Xiaoheng Liu

Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.

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Acta Biochimica et Biophysica Sinica•2025

pSTAT3 transactivates EGFR in maintaining EGFR protein homeostasis and EGFR-TKI resistance

Authors: Juan Ao, Junjie Fei, Guoqiang Wang, Wenhua Zhang, Shuhan Yu, Rongtian Guo, Mengmeng Niu, Hu Chen, Yang Cao, Zhi-Xiong Jim Xiao, Yong Yi

EGFR protein trafficking is critical for regulating multiple biological processes, including cell growth and survival. However, how EGFR protein homeostasis is maintained remains unclear. In this study, we show that a reduction in plasma membrane-associated EGFR triggers EGFR transcription by promoting pSTAT3 nuclear localization. Nucleus-localized pSTAT3 binds to the EGFR gene promoter to transactivate EGFR. Moreover, erlotinib, an EGFR tyrosine kinase inhibitor (TKI), can also increase pSTAT3 nuclear accumulation, resulting in increased EGFR transcription and erlotinib resistance. Importantly, pharmacological inhibition of pSTAT3 can significantly overcome the resistance of cancer cells to erlotinib. Together, these findings demonstrate that pSTAT3 is pivotal for maintaining EGFR protein homeostasis and suggest that activation of the pSTAT3-EGFR axis contributes to EGFR-TKI resistance.

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Acta Biochimica et Biophysica Sinica•2025

Primate-specific sperm lnc-CLCN7 reveals embryo quality in IVF

Authors: Xinrong Du, Rui Zheng, Sixian Wu, Qianhong Ma, Xudong Zhao, Xiaoliang Li, Wenming Xu

Long non-coding RNAs (lncRNAs) are an essential class of regulatory molecules that participate in diverse biological processes. However, whether sperm-derived lncRNAs from infertile men contribute to impaired embryo development during in vitro fertilization (IVF) remains unclear. In this study, we investigate the lncRNA expression profiles in sperm from asthenozoospermic patients with poor embryo development and explore their potential roles in early embryo development. Microarray analyses identify 993 differentially expressed lncRNAs in sperm samples from these patients, including 626 downregulated and 367 upregulated probes. Among them, an antisense transcript, lnc-CLCN7, is validated as the most significantly dysregulated lncRNA in an expanded cohort. In situ hybridization demonstrates that lnc-CLCN7 is localized in spermatogenic cells of primate testes and within the nuclei of HTR-8 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses reveal that lnc-CLCN7 is associated with the regulation of ion transport, ion homeostasis and related signaling pathways. Further experiments demonstrate that Lnc-CLCN7 directly binds to the histone modification H3K9me2/3 in HTR-8 cells and that its expression in sperm is modulated by oxidative stress induced by H2O2 treatment. Additionally, dysregulation of the glycolysis/gluconeogenesis and pyrimidine metabolism pathways in sperm is found to contribute to poor embryo development. Collectively, our findings identify Lnc-CLCN7 as an H3K9me2/3-binding, oxidative stress–responsive lncRNA that may serve as a potential biomarker for predicting poor embryo development in IVF and provide new insights into the molecular mechanisms linking sperm RNA regulation to embryo quality.

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Stem Cell Research & Therapy•2024

Glutamine-αKG axis affects dentin regeneration and regulates osteo/odontogenic differentiation of mesenchymal adult stem cells via IGF2 m6A modification

Authors: Qinglu Tian, Shiqi Gao, Siying Li, Mian Wan, Xin Zhou, Wei Du, Xuedong Zhou, Liwei Zheng, Yachuan Zhou

Background Multi-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate (αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc., while its role in m-ASCs still lack adequate research evidence. Methods We employed metabolomic analysis to explore the change pattern of metabolites during dental-pulp-derived m-ASCs differentiation. A murine incisor clipping model was established to investigate the influence of αKG on dental tissue repairment. shRNA technique was used to knockdown the expression of related key enzyme-dehydrogenase 1(GLUD1). RNA-seq, m6A evaluation and MeRIP-qPCR were used to dig into the underlying epigenetic mechanism. Results Here we found that the glutamine-αKG axis displayed an increased tendency along with the osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, same as expression pattern of GLUD1. Further, the key metabolite αKG was found able to accelerate the repairment of clipped mice incisor and promote dentin formation. Exogenous DM-αKG was proved able to promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, while the inhibition of glutamine-derived αKG level via GLUD1 knockdown had the opposite effect. Under the circumstance of GLUD1 knockdown, extracellular matrix (ECM) function and PI3k-Akt signaling pathway was screened out to be widely involved in the process with insulin-like growth factor 2 (IGF2) participation via RNA-seq. Inhibition of glutamine-αKG axis may affect IGF2 translation efficiency via m6A methylation and can be significantly rescued by αKG supplementation.

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Stem Cell Research & Therapy•2024

Xenogenous implanted dental follicle stem cells promote periodontal regeneration through inducing the N2 phenotype of neutrophils

Authors: Li Liu, Yuqi Wen, Liangrui Chen, Maoxue Li, Jialu Yu, Weidong Tian, Yafei Wu, Shujuan Guo

Background Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. Methods To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. Results In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type

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Acta Biochimica et Biophysica Sinica•2024

GroEL triggers NLRP3 inflammasome activation through the TLR/NF-ÎşB p-p65 axis in human periodontal ligament stem cells

Authors: Li Zhang, Mengmeng Duan, Xiaohua Pu, Huiling Zheng, Xinjie Ning, Ying Tu, Chunming Xu, Demao Zhang, Chengcheng Liu, Jing Xie

The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1β and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.

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Acta Biochimica et Biophysica Sinica•2024

Disruption of a DNA G-quadruplex causes a gain-of-function SCL45A1 variant relevant to developmental disorders

Authors: Yuxi Chen, Jiang Long, Sixian Wu, Yazhen Wei, Fei Yan, Qing Li, Jierui Yan, Nannan Zhang, Wenming Xu

SLC45A1 encodes a glucose transporter protein highly expressed in the brain. Mutations in SLC45A1 may lead to neurological diseases and developmental disorders, but its exact role is poorly understood. DNA G-quadruplexes (DNA G4s) are stable structures formed by four guanine bases and play a role in gene regulation and genomic stability. Changes in DNA G4s may affect brain development and function. The mechanism linking alterations in DNA G-quadruplex structures to SLC45A1 pathogenicity remains unknown. In this study, we identify a functional DNA G-quadruplex and its key binding site on SLC45A1 (NM_001080397.3: exon 2: c.449 G>A: p.R150K). This variant results in the upregulation of mRNA and protein expression, which may lead to intellectual developmental disorder with neuropsychiatric features. Mechanistically, the mutation is found to disrupt DNA G-quadruplex structures on SLC45A1, leading to transcriptional enhancement and a gain-of-function mutation, which further causes increased expression and function of the SLC45A1 protein. The identification of the functional DNA G-quadruplex and its effects on DNA G4s may provide new insights into the genetic basis of SLC45A1 pathogenicity and highlight the importance of DNA G4s of SLC45A1 in regulating gene expression and brain development.

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